The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae

Research output: Contribution to journal › Journal article › Research › peer-review

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The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. / Hansson Petersen, Camilla A; Alikhani, Nyosha; Behbahani, Homira; Wiehager, Birgitta; Pavlov, Pavel F; Alafuzoff, Irina; Leinonen, Ville; Ito, Akira; Winblad, Bengt; Glaser, Elzbieta; Ankarcrona, Maria; Petersen, Anna Camilla Hansson.

In: Proceedings of the National Academy of Sciences USA (PNAS), Vol. 105, No. 35, 2008, p. 13145-50.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hansson Petersen, CA, Alikhani, N, Behbahani, H, Wiehager, B, Pavlov, PF, Alafuzoff, I, Leinonen, V, Ito, A, Winblad, B, Glaser, E, Ankarcrona, M & Petersen, ACH 2008, 'The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae', Proceedings of the National Academy of Sciences USA (PNAS), vol. 105, no. 35, pp. 13145-50. https://doi.org/10.1073/pnas.0806192105

APA

Hansson Petersen, C. A., Alikhani, N., Behbahani, H., Wiehager, B., Pavlov, P. F., Alafuzoff, I., Leinonen, V., Ito, A., Winblad, B., Glaser, E., Ankarcrona, M., & Petersen, A. C. H. (2008). The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proceedings of the National Academy of Sciences USA (PNAS), 105(35), 13145-50. https://doi.org/10.1073/pnas.0806192105

Vancouver

Hansson Petersen CA, Alikhani N, Behbahani H, Wiehager B, Pavlov PF, Alafuzoff I et al. The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proceedings of the National Academy of Sciences USA (PNAS). 2008;105(35):13145-50. https://doi.org/10.1073/pnas.0806192105

Author

Hansson Petersen, Camilla A ; Alikhani, Nyosha ; Behbahani, Homira ; Wiehager, Birgitta ; Pavlov, Pavel F ; Alafuzoff, Irina ; Leinonen, Ville ; Ito, Akira ; Winblad, Bengt ; Glaser, Elzbieta ; Ankarcrona, Maria ; Petersen, Anna Camilla Hansson. / The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. In: Proceedings of the National Academy of Sciences USA (PNAS). 2008 ; Vol. 105, No. 35. pp. 13145-50.

Bibtex

@article{7d9fbd83cc5743d78635fdeb0f381122,
title = "The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae",
abstract = "The amyloid beta-peptide (Abeta) has been suggested to exert its toxicity intracellularly. Mitochondrial functions can be negatively affected by Abeta and accumulation of Abeta has been detected in mitochondria. Because Abeta is not likely to be produced locally in mitochondria, we decided to investigate the mechanisms for mitochondrial Abeta uptake. Our results from rat mitochondria show that Abeta is transported into mitochondria via the translocase of the outer membrane (TOM) machinery. The import was insensitive to valinomycin, indicating that it is independent of the mitochondrial membrane potential. Subfractionation studies following the import experiments revealed Abeta association with the inner membrane fraction, and immunoelectron microscopy after import showed localization of Abeta to mitochondrial cristae. A similar distribution pattern of Abeta in mitochondria was shown by immunoelectron microscopy in human cortical brain biopsies obtained from living subjects with normal pressure hydrocephalus. Thus, we present a unique import mechanism for Abeta in mitochondria and demonstrate both in vitro and in vivo that Abeta is located to the mitochondrial cristae. Importantly, we also show that extracellulary applied Abeta can be internalized by human neuroblastoma cells and can colocalize with mitochondrial markers. Together, these results provide further insight into the mitochondrial uptake of Abeta, a peptide considered to be of major significance in Alzheimer's disease.",
keywords = "Amyloid beta-Peptides, Animals, Cell Line, Tumor, Endocytosis, Endopeptidase K, Extracellular Space, Flow Cytometry, Fluorescent Antibody Technique, Humans, Male, Microscopy, Immunoelectron, Mitochondria, Mitochondria, Liver, Mitochondrial Proteins, Neuroblastoma, Peptides, Protein Transport, Rats, Rats, Sprague-Dawley",
author = "{Hansson Petersen}, {Camilla A} and Nyosha Alikhani and Homira Behbahani and Birgitta Wiehager and Pavlov, {Pavel F} and Irina Alafuzoff and Ville Leinonen and Akira Ito and Bengt Winblad and Elzbieta Glaser and Maria Ankarcrona and Petersen, {Anna Camilla Hansson}",
year = "2008",
doi = "10.1073/pnas.0806192105",
language = "English",
volume = "105",
pages = "13145--50",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "The National Academy of Sciences of the United States of America",
number = "35",

}

RIS

TY - JOUR

T1 - The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae

AU - Hansson Petersen, Camilla A

AU - Alikhani, Nyosha

AU - Behbahani, Homira

AU - Wiehager, Birgitta

AU - Pavlov, Pavel F

AU - Alafuzoff, Irina

AU - Leinonen, Ville

AU - Ito, Akira

AU - Winblad, Bengt

AU - Glaser, Elzbieta

AU - Ankarcrona, Maria

AU - Petersen, Anna Camilla Hansson

PY - 2008

Y1 - 2008

N2 - The amyloid beta-peptide (Abeta) has been suggested to exert its toxicity intracellularly. Mitochondrial functions can be negatively affected by Abeta and accumulation of Abeta has been detected in mitochondria. Because Abeta is not likely to be produced locally in mitochondria, we decided to investigate the mechanisms for mitochondrial Abeta uptake. Our results from rat mitochondria show that Abeta is transported into mitochondria via the translocase of the outer membrane (TOM) machinery. The import was insensitive to valinomycin, indicating that it is independent of the mitochondrial membrane potential. Subfractionation studies following the import experiments revealed Abeta association with the inner membrane fraction, and immunoelectron microscopy after import showed localization of Abeta to mitochondrial cristae. A similar distribution pattern of Abeta in mitochondria was shown by immunoelectron microscopy in human cortical brain biopsies obtained from living subjects with normal pressure hydrocephalus. Thus, we present a unique import mechanism for Abeta in mitochondria and demonstrate both in vitro and in vivo that Abeta is located to the mitochondrial cristae. Importantly, we also show that extracellulary applied Abeta can be internalized by human neuroblastoma cells and can colocalize with mitochondrial markers. Together, these results provide further insight into the mitochondrial uptake of Abeta, a peptide considered to be of major significance in Alzheimer's disease.

AB - The amyloid beta-peptide (Abeta) has been suggested to exert its toxicity intracellularly. Mitochondrial functions can be negatively affected by Abeta and accumulation of Abeta has been detected in mitochondria. Because Abeta is not likely to be produced locally in mitochondria, we decided to investigate the mechanisms for mitochondrial Abeta uptake. Our results from rat mitochondria show that Abeta is transported into mitochondria via the translocase of the outer membrane (TOM) machinery. The import was insensitive to valinomycin, indicating that it is independent of the mitochondrial membrane potential. Subfractionation studies following the import experiments revealed Abeta association with the inner membrane fraction, and immunoelectron microscopy after import showed localization of Abeta to mitochondrial cristae. A similar distribution pattern of Abeta in mitochondria was shown by immunoelectron microscopy in human cortical brain biopsies obtained from living subjects with normal pressure hydrocephalus. Thus, we present a unique import mechanism for Abeta in mitochondria and demonstrate both in vitro and in vivo that Abeta is located to the mitochondrial cristae. Importantly, we also show that extracellulary applied Abeta can be internalized by human neuroblastoma cells and can colocalize with mitochondrial markers. Together, these results provide further insight into the mitochondrial uptake of Abeta, a peptide considered to be of major significance in Alzheimer's disease.

KW - Amyloid beta-Peptides

KW - Animals

KW - Cell Line, Tumor

KW - Endocytosis

KW - Endopeptidase K

KW - Extracellular Space

KW - Flow Cytometry

KW - Fluorescent Antibody Technique

KW - Humans

KW - Male

KW - Microscopy, Immunoelectron

KW - Mitochondria

KW - Mitochondria, Liver

KW - Mitochondrial Proteins

KW - Neuroblastoma

KW - Peptides

KW - Protein Transport

KW - Rats

KW - Rats, Sprague-Dawley

U2 - 10.1073/pnas.0806192105

DO - 10.1073/pnas.0806192105

M3 - Journal article

C2 - 18757748

VL - 105

SP - 13145

EP - 13150

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 35

ER -

ID: 41992151